期刊
LIFE SCIENCES
卷 232, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2019.116632
关键词
miRNA-181a; Inflammation; Regulatory T cell; C-Fos; Myocardial infarction; Bioinformatics
资金
- Natural Science Foundation of China [81700392]
- Funds for Jiangsu Provincial Key Medical Discipline [ZDXKB2016013]
- Key Projects of Science and Technology of Jiangsu Province [BE2016607]
- Natural Science Foundation of Jiangsu Province - Youth Fund Project [BK20150106]
- Funds for Distinguished Young Scientists in Nanjing [JQX15002]
- Programs of the Science Foundation in Nanjing [QRX17113, YKK17085, YKK17095]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX18_1462]
- Nanjing Health Youth Talent Training Project in 13th Five-Year [QRX17113]
Aims: The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. Main methods: Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. Key findings: miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. Significance: We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.
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